Prostate Cancer
Conditions
Keywords
NDGA, Prostate Cancer
Brief summary
This is a Phase II, single center study measuring the pharmacokinetic parameters of NDGA administration and assessing the proportion of patients who experience a 50% decline in PSA.
Detailed description
This study is a phase II trial of NDGA in patients with hormone-sensitive non-metastatic prostate cancer with a pharmacokinetics component. The first six patients enrolled will be treated with a single 750 mg dose of oral NDGA on day -7 with measurement of pharmacokinetic parameters over eight hours after the dose, then begin treatment with 2000 mg of oral NDGA daily. Every four weeks, measurement of pharmacokinetic parameters at steady state will be done for all patients. All patients will continue dosing with NDGA and will be followed for PSA response and for safety. Measurement of pharmacokinetics for a 750 mg dose has been chosen to evaluate levels with the dosage that patients will be taking at one time point during the day (this is roughly one-third of the daily dose, which is administered in three divided doses).
Interventions
DRUGNordihydroguaiaretic Acid (NDGA)
NDGA 2000mg daily
Sponsors
Insmed Incorporated
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Rising prostate-specific antigen (PSA) value after local therapy with a PSA doubling time (PSADT) between 6 and 24 months (four or more readings at least two weeks apart within the last six months) * Prior definitive therapy for prostate cancer consisting of one of the following: 1. External beam radiotherapy with or without hormone therapy 2. Brachytherapy with or without pelvic external beam radiation or hormone therapy 3. Radical prostatectomy with or without adjuvant or salvage radiation therapy * PSA \> 1 ng/ml, which has risen serially on two determinations at least one week apart * Progressive disease by Phoenix consensus definition for patients who have undergone primary radiation therapy (PSA nadir + 2 ng/mL) * No metastatic disease * Prior adjuvant or neoadjuvant androgen deprivation is permitted, provided: 1. \> 6 months since last day of effective androgen deprivation 2. Testosterone \> 250 ng/dL 3. Patient is not on intermittent androgen deprivation * Karnofsky performance status (KPS) of \> 70% * Liver Function Tests are within normal range * Glycated hemoglobin (HgA1c) \< 6% * Patients must be four weeks from major surgery or radiotherapy to be eligible
Exclusion criteria
* Presence of another active malignancy other than prostate cancer, or treated squamous/basal cell carcinoma of the skin. Concomitant medical condition which would make it undesirable, in the physician's opinion, for the patient to participate in the protocol or would jeopardize compliance with the protocol requirements * Diabetes mellitus, unless diet-controlled * Must be off saw palmetto, pomegranate juice, finasteride, or any herbal agent intended to lower PSA for \> 4 weeks. Baseline PSADT calculation must occur off of these agents * Patients may not have evidence of local-only recurrence of prostate cancer * No history of liver disease, including Hepatitis B or C, alcoholic liver disease, or autoimmune liver disease. A prior history of Hepatitis A is allowed provided that baseline liver function tests are within normal limits * Patients with castration resistant prostate cancer are ineligible (prostate cancer which has progressed on androgen deprivation therapy with a Luteinizing hormone-releasing hormone (LHRH)-agonist or orchiectomy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prostate Specific Antigen (PSA) Response According to Consensus Criteria | Monthly, up to 29 months | Participants who experienced a PSA decline of at least 50%, confirmed by a second PSA value 4 or more weeks later. The reference PSA for decline was a PSA measured within 2 weeks of beginning study treatment. If at most 1 PSA response was observed among the first 12 patients, then accrual would stop and the trial would close for futility. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NDGA Nordihydroguaiaretic Acid (NDGA) 2000mg given orally daily in 3 divided doses (750mg in the morning and in the evening, and 500mg at midday) over a 28-day cycle. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | NDGA |
|---|---|
| Age, Continuous | 67.5 years |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Prostate Specific Antigen (PSA) Response According to Consensus Criteria
Participants who experienced a PSA decline of at least 50%, confirmed by a second PSA value 4 or more weeks later. The reference PSA for decline was a PSA measured within 2 weeks of beginning study treatment. If at most 1 PSA response was observed among the first 12 patients, then accrual would stop and the trial would close for futility.
Time frame: Monthly, up to 29 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NDGA | Prostate Specific Antigen (PSA) Response According to Consensus Criteria | 0 participants |
Post Hoc
Change in Prostate Specific Antigen Doubling Time (PSADT)
PSADT was calculated using the formula natural log 2 divided by the slope of the natural log of the PSA versus time. Pretreatment PSADT was calculated using a minimum of 3 values; end of study PSADT incorporated all measured PSA values on study starting Cycle 2-Day 1 until the patient was removed from the study.
Time frame: Cycle 2 through end of treatment (up to 29 months)
Population: At the time of PSADT calculations, one participant was still on study at 29 months, and 11 participants' time on study had ranged from 2-19 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NDGA | Change in Prostate Specific Antigen Doubling Time (PSADT) | 17 percentage change |
Post Hoc
Disease Progression at End of Study
End-of-study imaging was assessed for disease progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: \* Progressive Disease (PD)=At least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Baseline, End of treatment (2-19 cycles)
Population: At the time of calculation, 1 patient was still on study after 29 cycles
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NDGA | Disease Progression at End of Study | 0 participants |
Post Hoc
PSA Decline
Number of participants experiencing PSA decline during the first 3 treatment cycles
Time frame: Baseline; Monthly, up to 29 months after beginning treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NDGA | PSA Decline | 7 participants |